Tailoring medicine by reading the code for life

Rebecca Bellone, PhD, became a geneticist to understand the causes of Appaloosa coat patterns in horses.

Rebecca Bellone, PhD, and an Appaloosa with congenital inpatient night blindness

Her work helped identify associations between spotting and congenital stationary night blindness caused by abnormal signal transmission from cells in the retina. Dr. Bellone, director of the University of California-Davis’ veterinary genetic laboratory and professor of population health and reproduction, attributes part of her team’s success in identifying the genetic cause of the disease to access to the horse’s reference genome.

The horse was among the first animals with complete genome sequences after the first human genome was published. So Dr. Bellone and her team compare genes between humans and horses.

The team found that in Appaloosa horses with night blindness, a gene known as TRPM1 was downregulated for the functioning of the calcium ion channel.

“This work led scientists studying human night blindness to consider this gene to be the cause of night blindness in humans,” she said. “It turns out that the gene has more mutations that cause night blindness in humans than any other genes they discovered earlier.”

Dr. Bellone said the publication of a human genome 20 years ago changed the ability of the scientific community to identify genetic causes of disease and animal traits, and to enable genetic testing for animal breeding and disease management. Access to a published human genome led to work on animal genomes for comparative genomics, which has helped reveal the role of genetic sequences across species and advance human and veterinary medicine, she said.

“Veterinary medicine really benefited from the push into comparative genomics because then there was a push into sequencing the genomes of other species like dogs and horses,” said Dr. Bellone. “Having these genomes and comparing them to humans has really accelerated the speed at which we can make discoveries to find causes of genetic diseases, and that has made diagnostic tests possible for genetic diseases in all species.”

An important milestone

On February 12, 2001, the International Human Genome Sequencing Consortium announced the publication of a draft sequence and initial analysis of the human genome in the journal Nature. A wealth of information was gleaned from the initial analysis of human genomic design, according to the National Institutes of Health. For example, the number of human genes was originally estimated to be around 35,000. This was later revised to around 20,000.

The tools and techniques of the Human Genome Project have given the world ever faster access to genetic information at drastic price reductions, and the collective information on genetic links to disease and gene function makes this information accessible and useful to clinicians.

Leslie A. Lyons, PhD, director of the Feline Genetics and Comparative Medicine Laboratory at the University of Missouri College of Veterinary Medicine and professor of comparative medicine, said the Human Genome Project provided the technologies to better sequence and analyze genomics and genomes Providing the infrastructure to store and manipulate this data.

“Everything we have learned from humans, including the advancement of technology, has been carried over into what we do with our cats and dogs and even with our farm animals,” said Dr. Lyons.

Today, entire genome sequencing, available at the University of Missouri’s Veterinary Health Center, can identify the genetic causes of hereditary diseases within days to weeks of a blood sample being drawn. The cost of sequencing an animal’s genome has dropped below the cost of an MRI, she said.

“We can now do precision medicine in cats thanks to what has been done in the Human Genome Project,” said Dr. Lyons.

Cost, time to immerse yourself in the sequence

In his 2021 book, Genome Odyssey, Euan Angus Ashley, Professor of Medicine and Genetics at Stanford University, stated that the Human Genome Project had a budget of $ 3 billion and in 2001 published a draft of the human genome at Stanford sequenced a genome for $ 40,000 in a week, which is already a million times the price.

In August 2021, the estimated cost of sequencing a human genome was less than $ 600, according to the NIH National Human Genome Research Institute.

Dr. Ashley later wrote in his book that “a doctor today can order a genome for a patient with a rare disease almost as easily as a cholesterol test.”

“Health insurance companies are increasingly listing it as a covered benefit and recognizing that transformative insights can emerge,” he wrote. “Some health systems even offer genetic sequencing as part of preventative care – a way of detecting disease risks in advance of the disease.”

Adam Boyko, PhD, is an adjunct professor and researcher in canine genetics at Cornell University and a co-founder of canine DNA testing company Embark. He said he heard thanks from pet owners about every two weeks for health information revealed in company tests that help with grooming.

For example, in 2019 his company’s genetic testing found hemophilia in a dog, Wolfy, and that diagnosis may have saved the dog’s life. Another dog attacked Wolfy and pierced his neck a month later, and the genetic results helped treatment by his regular vet and the vets who looked after him at an emergency and specialty hospital for four days, said Dr. Boyko.

I would expect the entire genome sequencing to be a routine for you to check out as part of the health care of our pets including horses, cats and dogs.

Leslie A. Lyons, PhD, director of the Feline Genetics and Comparative Medicine Laboratory at the University of Missouri College of Veterinary Medicine and Professor of Comparative Medicine

Dr. Doug Antczak, a veterinary scientist and professor of equine medicine at Cornell, said the human genome project helped build a large workforce with expertise in genome sequencing and a wealth of scientific tools for this purpose.

“The Human Genome Project has created a tremendous capacity for decoding genomes,” he said.

Using comparative genetics, researchers can find out which genes are conserved in mammals, vertebrates, and even fruit flies – information that will help improve health.

Dr. Antczak was part of a global group of scientists who began targeted work on the horse genome in 1995 in the hope of one day being able to create a rough genome map.

“More and more technology came online and the cost kept falling, so we could expand our ambitions and raise our goals so that we eventually had the entire equine genome sequenced,” said Dr Antczak.

Sequencing the first horse genome required six months of continuous sequencing through 100 machines, he said. Now you can do this on one machine in just a few days.

“It is unimaginable how efficient this process has become,” he said. “It has exceeded our ability to truly understand and process the information we receive.”

Genetic testing is also now being used to eradicate genetic diseases that Dr. Antczak are a form of preventive medicine. For example, Arab horse owners now have access to a $ 50 test that will determine if their horses are carriers of the gene for a severe combined immunodeficiency disease that causes horses to be born without a functioning immune system.

Applications can become routine

Within the next decade, Dr. Lyons said genetic testing panels will become common, perhaps when animals are born, to let owners know about deficiencies and health risks. She also wants whole genome sequencing to be part of routine health care, just as she expects it to be part of cutting edge health care for humans.

“I would expect the whole genome sequencing to be a routine that you can review as part of the health care of our pets, including horses, cats and dogs,” she said.

The price of sequencing will continue to drop, she said, and health insurers could see benefits in paying for genome tests that could be used for preventive medicine, which would make general health care more efficient.

Dr. Ashley from Stanford predicts in his book that genomes will be cheaper and faster to produce. More importantly, genome data is becoming more accurate and “we are starting to shed a much stronger light on the dark corners of the genome”.

These advances include bespoke medicine that uses genetic data to predict and prevent disease risk, real-time health monitoring, detection and identification of pathogens, and studies showing how pathogens have spread. For example, he described genomics as the heavy artillery in the fight against SARS-CoV-2, with the rapid availability of the virus sequence that is used to create genetic tests for infection, uncover the history of the virus’s spread around the world, and one Developing vaccine candidates at unprecedented speed.

Dr. Antczak noted that genomics researchers are now identifying the control mechanisms in non-gene coding areas of the genome and are working to understand how genes are controlled at various stages of animal development, health, and disease.

Dr. Boyko anticipates that more veterinarians will adopt genetic testing as part of their practice in the next 10 years. Genetic markers of drug sensitivities could be considered when a veterinarian is treating a dog for cancer, and DNA testing for puppies could dramatically alter other clinical outcomes for many dogs, he said.

Dr. Bellone cited ongoing work at UC-Davis led by Dr. Carrie Finno, director of the Center for Equine Health to identify genetic causes of disease in horses under controlled conditions, a project that Dr. Bellone sees precision medicine as a trailblazer.

Any veterinarian can take part in precision medicine, said Dr. Lyons.

“All your private practice veterinarian needs to do is be able to get a good blood sample and have the right interest,” she said.